Clinical, Molecular, Functional, and Structural Characterization of CYP17A1 Mutations in Brazilian Patients with 17-Hydroxylase Deficiency
Horm Metab Res 2020; 52: 186-193 DOI: 10.1055/a-1100-706617-Hydroxylase-deficiency (17OHD) is a rare form of congenital adrenal
hyperplasia. The aim of the work was to study clinical, biochemical, and the
follow up of 17OHD patients and evaluate the function and structure of
CYP17A1 mutations. Brazilian patients (three 46, XX and four 46,
XY; 17±1.9 years) with combined 17-hydroxylase/17,20-lyase
deficiency were evaluated. CYP17A1 gene was sequenced. Functional
analysis was performed transfecting COS7 cells, which were exposed to
progesterone or 17α-hydroxypregnolone substrates. Hormones were
determined by RIA or LC-MS/MS. Three-dimensional structural modeling
was performed by Modeller software. All patients presented prepubertal
female external genitalia, primary amenorrhea, hypergonadotrophic
hypogonadism, hypokalemic hypertension, decreased cortisol, and increased
ACTH and corticosterone levels. Five patients presented previously described
mutations: p.W406R/p.W406R,
IVS2–2A>C/p.P428L, and p.P428L/p.P428L. Two
patients presented the compound heterozygous
p.G478S/p.I223Nfs*10 mutations, whose CYP17A1 activity and
the three dimensional structural modeling are originally studied in this
paper. CYP17A1 activity of p.G478S was 13 and 58% against
...
Source: Hormone and Metabolic Research - Category: Endocrinology Authors: Coeli-Lacchini, Fernanda Borchers Mermejo, Livia M. Bodoni, Aline Faccioli Elias, Lucila Leico Kagohara Silva Jr, Wilson Ara újo Antonini, Sonir R. Moreira, Ayrton C. de Castro, Margaret Tags: Endocrine Care Source Type: research
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